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Stress is a ubiquitous challenge in modern societies. Symptoms range from mood swings and cognitive impairment to autonomic symptoms. This study explores the link between work-related stress and the neurobiological element of brain processing, testing the hypothesis that patients with occupational stress have altered cerebral glucose consumption compared to healthy controls. The participants' present conditions were evaluated using an adapted WHO SCAN interview. Neural activity at rest was assessed by positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose. Participants were genotyped for the Val158Met polymorphism of the COMT gene, believed to influence stress resilience. This study included 11 women with work-related stress and 11 demographically comparable healthy controls aged 28–62 years, with an average of 46.2 years. The PET scans indicated clusters of decreased glucose consumption primarily located in the white matter of frontal lobe sub-gyral areas in stress patients. COMT Val158Met polymorphism detection indicated no immediate relation of the homozygous alleles and stress resilience; however, healthy controls mainly had the heterozygous allele. In conclusion, the results support that work-related stress does affect the brain in the form of altered glucose metabolism, suggesting neurobiological effects could be related to white matter abnormalities rather than gray matter deterioration. Genotyping indicates a more complex picture than just that of the one type being more resilient to stress. Further studies recruiting a larger number of participants are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

Self-commitments and increasing legal requirements lead to the compulsion to reduce carbon dioxide emissions in commercial aerospace. One viable approach is the reduction of structural mass, that would reduce emissions for every flight. This is especially true for high cadence singe aisle aircrafts. However, high quantities are required in this segment. To achieve these goals the newly developed low-melt Poly-Aryl-Ether-Ketone (LM-PAEK), a high-performance carbon fiber-reinforced thermoplastic composite was chosen to build a full-scale multi-functional fuselage demonstrator (MFFD) in order to delevelop an automated process that shows these savings. Single-step automated Fiber Placement (AFP) with in-situ consolidation offers distinct advantages in this field with its short curing times and especially by eliminating high amounts of waste otherwise caused by vacuum bagging and related tasks for post-consolidation in an autoclave. In order to ready this technology for future aircraft production this paper demonstrates how the processing window for LM-PAEK tape (TC1225) provided by TORAY was established. By closely linking robot and end-effector data with positionally accurate thermocouple measurements, the determined mechanical properties at coupon level and micro-sections of the manufactured specimens can be precisely correlated. This holistic approach is independent of the placement equipment and may enable global comparability within the community working in the field of thermoplastic AFP. In conclusion the procedure is evaluated and possible simplifications are discussed. [ABSTRACT FROM AUTHOR]

Highlights: 800 shoulder MRIs were retrospectively evaluated for humeral, glenoidal and latero-glenoidal humeral offset, as well as cortical and humeral shaft axis offset. Significantly higher values for all analysed offset parameters were found in male shoulder joints compared to female shoulder joints. Significant side-specific differences were found for humeral, glenoidal and latero-glenoidal humeral offset. A correlation of the offset parameters with age or the osteoarthritis grade exist only for cortical offset. These results should be considered in shoulder diagnostics and surgery. Background: Humeral offset (HO) and glenoidal offset (GO) are important morphological parameters in diagnostics and therapy for shoulder pathologies. However, physiological reference values have not yet been sufficiently determined. The aim of the present study was to establish physiological reference values for shoulder offset parameters (SOPs). Methods: MRI images of the shoulder joints of 800 patients (mean age: 50.13 years [±16.01]) were analysed retrospectively. HO, GO, lateral glenoidal humeral offset (LGHO), humeral shaft axis offset (HAO) and cortical offset (CO) were measured. SOPs were examined for associations with age, gender, side and osteoarthritis. Results: The mean HO was 26.19 (±2.70), the mean GO was 61.79 (±5.67), the mean LGHO was 54.49 (±4.69), the mean HAO was 28.17 (±2.82) and the mean CO was 16.70 (±3.08). For all SOPs, significantly higher values were measured in male shoulders. There was a significantly (p < 0.001) higher mean value for HO, GO and LGHO in right shoulders. There was a significant correlation between age and LGHO, and HAO and CO, but not between age and HO or GO. Shoulders with osteoarthritis and non-osteoarthritis did not differ in the mean value of HO, GO, LGHO and HAO, except for CO (p = 0.049). Conclusion: Reference values for SOPs in the adult shoulder joint were determined for the first time. Significant gender-specific differences were found for all measured SOPs. In addition, it was seen that for some SOPs, the joint side and the patient's age has to be taken into account in shoulder diagnostics and surgery. [ABSTRACT FROM AUTHOR]

Purpose: No reference material exists on the scope of long-term problems in novel spinal pain opioid users. In this study, we evaluate the prevalence and long-term use of prescribed opioids in patients of the Spinal Pain Opioid Cohort. Methods: The setting was an outpatient healthcare entity (Spine Center). Prospective variables include demographics, clinical data collected in SpineData, and The Danish National Prescription Registry. Patients with a new spinal pain episode lasting for more than two months, aged between 18 and 65 years, who had their first outpatient visit. Based on the prescription of opioids from 4 years before the first spine center visit to 5 years after, six or more opioid prescriptions in a single 1-year interval fulfilled the main outcome criteria Long-Term Opioid Therapy (LTOT). Results: Overall, of 8356 patients included in the cohort, 4409 (53%) had one or more opioid prescriptions in the registered nine years period. Of opioid users, 2261 (27%) were NaiveStarters receiving their first opioid prescription after a new acute pain episode; 2148(26%) PreStarters had previously received opioids. The prevalence of LTOT in PreStarters/NaiveStarters was 17.2%/11.2% in their first outpatient year. Similar differences between groups were seen in all follow-up intervals. In the last follow-up year, LTOT prevalence in Prestarters/NaiveStarters was 12.5%/7.0%. Conclusions: Previous opioid treatment—i.e., before a new acute spinal pain episode and referral to a Spine Center—doubled the risk of LTOT 5 years later. The results underscore clinicians' obligation to carefully and individually weigh the benefits against the risks of prescribing opioid therapy. Level of evidence I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding. [ABSTRACT FROM AUTHOR]

Purpose: Burnout and workplace violence (WPV) have been associated in cross-sectional studies, but longitudinal studies with solid methods and adequate sample sizes are lacking. This study investigates whether WPV increases burnout symptoms during a 12-month period. Methods: Questionnaire data were collected on 1823 social educators at baseline and 12-month follow-up, coupled with additionally 12 monthly text-message surveys on exposure to WPV. Using general linear modelling for repeated measures, we estimated change over time in burnout symptoms in three WPV exposure groups (none, low, high). Results: A time by exposure to WPV interaction existed for development of burnout; F(2) = 7.2, p = 0.001 η2 = 0.011. Burnout increased significantly within the group of low exposure; F(1) = 6.8, p = 0.01 and high exposure; F(1) = 6.7 p = 0.001, but not within the non-exposed F(1) = 2.1 p = 0.15. At follow-up, both the low exposed and high exposed had significantly higher levels of burnout compared to the non-exposed. Conclusion: Exposure to WPV increases level of burnout within a 12-month period. We propose that assessment of burnout in future studies should utilize instruments capable of detecting small changes. We further propose that prevention against employee burnout could be improved using monitoring targeted at employees exposed to WPV. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of psychological stress has previously been estimated based on self-reported questionnaires. This study aimed to investigate the prevalence of persons who contact the general practitioner (GP) for psychological stress and to explore associations between psychological stress and characteristics relating to the patient, the GP, and area-specific socioeconomic factors. Design: Cross-sectional computer assisted journal audit. Setting: General practice in the Region of Southern Denmark. Subjects: Patients aged 18-65 years with a consultation during a six-month period that was classified with a stress-related diagnosis code. Main outcome measures: Six months prevalence of GP-assessed psychological stress and characteristics relating to the patient, the GP, and area-specific socioeconomic factors. Results: Fifty-six GPs (7% of the invited) identified 1066 patients considered to have psychological stress among 51,422 listed patients. Accordingly, a 2.1% six months prevalence of psychological stress was estimated; 69% of cases were women. High prevalence of psychological stress was associated with female sex, age 35-54 years, high education level and low population density in the municipality, but not with unemployment in the municipality or household income in the postal district. GP female sex and age <50 years, few GPs in the practice and few patients per GP were also associated with a higher prevalence of psychological stress. Conclusions: A total of 2% of the working-age population contacted the GP during a six-month period for psychological stress. The prevalence of psychological stress varies with age, sex and characteristics of both the regional area and the GP. Key points:   Psychological stress is a leading cause of days on sick leave, but its prevalence has been based on population surveys rather than on assessment by health care professionals.   • This study found that during six months 2.1% of all working-age persons have at least one contact with the GP regarding psychological stress.   • The six months prevalence of psychological stress was associated with patient age and sex, GP age and sex, practices’ number of GPs and patients per GP, and area education and urbanization level. [ABSTRACT FROM AUTHOR]

This study investigated whether factors related to bodily contact between health care workers and patients were associated with patient-initiated violence. This cross-sectional study surveyed 496 Danish health care workers measuring patient-initiated violence, use of assistive devices, body mass index, physical exertion, frequency of patient transfers, psychosocial work environment, gender, age, and seniority. Associations were modeled using logistic regression analyses using patient-initiated violence as the outcome. Twenty-five percent of the respondents had experienced physical or verbal violence during the past year. Infrequent use of assistive devices, high physical strain, and severe obesity all significantly increased the risk of physical violence (risk ratio [RR] = 1.18, RR = 1.18, and RR = 1.16, respectively), whereas only the lack of assistive device use significantly increased the risk of verbal violence (RR = 1.13 and RR = 1.08). Consistent use of assistive devices appears to reduce the risk of patient-initiated violence. Managers should require the use of assistive devices when designing work processes for patient transfers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Coping with regret has a substantial impact on wellbeing and mental health, but has rarely been investigated in an occupational setting. OBJECTIVE: To translate the Regret Coping Scale for Health-Care Professionals (RCS-HCP) and explore internal consistency, construct-, criterion- and predictive validity. METHODS: The instrument was translated using forward- back method. The qualities were evaluated with a sample of 2758 social educators using exploratory and confirmatory factor analysis as well as Cronbach’s alpha, Pearson correlation, and multivariable regression. RESULTS: The translated instrument showed a trend similar to the original instrument. A 10-item version resulted from the research being reported. The reduced RCS-HCP showed improved fit (Full model, 15 items); CFI = 0.91, TLI = 0.89, RMSEA = 0.66, PClose = 0.000 and BIC = 1392 vs. (Reduced instrument, 10 items); CFI = 0.97, TLI = 0.96, RMSEA = 0.05, PClose = 0.499 and BIC 307. This instrument had acceptable internal consistency for short scales (Cronbach’s alpha = 0.65, 0.69 and 0.84 respectively). The subscales correlated as expected with measures of health and occupational factors, coefficient ranging from 0.182 to 0.399. Also, the RCS-HCP predicted stress three month later ΔF[3,2747] = 15.1, p < 0.001, but with very small effect ΔR2 = 0.01, p≤0.001. CONCLUSIONS: The 10-item Danish version of the RCS-HCP is a valid instrument for measuring coping with regret in health related work. [ABSTRACT FROM AUTHOR]

Background As pesticide use is increasing and proper handling training is lacking, exposure to pesticides and intoxications are an important public health problems among farmers in developing countries. This study describes pesticide use among farmers and compares symptoms of possible acute intoxication and Erythrocyte Acetylcholinesterase(AChE) levels among vegetable farmers with a control group of blood donors in Nepal. Methods A cross-sectional study was carried out among 90 pesticide-exposed farmers and a control group of 90 blood donors. Participants were randomly selected and data were gathered through questionnaires, observation and blood test. Chi-square test, logistic regression and Student's t-test were used for data analysis to describe pesticide use and compare symptoms and AChE levels between the two groups. This study was approved by Nepal Health Research Council. Results The majority of pesticides used were WHO class II, classified as moderately hazardous. The mean numbers of personal protective equipment used by farmers were 2.22 (95% CI: 1.89; 2.54). Out of five hygienic practices asked, farmers followed 3.63 (95% CI: 3.40; 3.86) hygienic practices on the average. Farmers reported more symptoms of possible pesticide intoxication in the past month than did controls, mean 5.47 (95% CI: 4.70; 6.25) versus 2.02 (95% CI: 1.63; 2.40) (p < 0.05). The mean haemoglobin-adjusted AChE(Q) was significantly lower among farmers compared to controls, 28.92 (95% CI: 28.28; 29.56) U/g versus 30.05 (95% CI: 29.51; 30.60) U/g, (p = 0.01). The risk of a farmer having lower Q level was about 3 times (OR = 2.95; 95% CI: 1.16; 7.51) greater than controls. Conclusion Nepalese farmers exposed to pesticides have significantly more symptoms of possible pesticide intoxication than a control group of healthy individuals. A lower mean haemoglobin- adjusted AChE level was seen among farmers compared to the controls. The use of highly toxic pesticides, inadequate use of personal protective equipment and poor hygienic practices might explain the reason for symptoms of pesticide intoxication and a lower AChE level among farmers. Education and information of farmers should be undertaken to remediate these problems. [ABSTRACT FROM AUTHOR]

Purpose: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. Methods: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain outcomes: acute, prolonged and chronic pain. Results: Mouse time, even at low levels, was associated with acute pain in a similar way for all the examined regions. There were no exposure-response threshold patterns. Keyboard time had no effect. Mouse and keyboard sustained activity, speed and micropauses were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. Conclusion: Computer work was not related to the development of prolonged or chronic pain. Mouse time was associated with acute distal arm pain, but the impact was quite small. [ABSTRACT FROM AUTHOR]

2,2'-Bipyridines are among the most widely used classes of chelating ligands that have found applications in the fields of coordination chemistry, supra-, nano- and macromolecular chemistry, analytical and photochemistry, but also in asymmetric synthesis and natural product chemistry. Hence, there is a huge demand for efficient synthetic approaches to functionalized derivatives. Modern cross-coupling procedures have been proven to be particularly effective in this context. This critical review will give an overview about the advances made so far focussing mainly on cross-coupling reactions with tin, zinc and boron compounds for the achievement of interesting, versatile and unusual substitution patterns (156 references). [ABSTRACT FROM AUTHOR]

BACKGROUND: Endoscopic ultrasound (EUS) can reliably diagnose and stage pancreatic cancer but is less competent for the differentiation between vascular compression (VC) and invasion (VI).AIM: Prospective comparison of linear EUS with/without three-dimensional (3D) EUS for vessel involvement in pancreatic cancer to evaluate the feasibility of linear 3D ultrasound.MATERIAL AND METHODS: Linear echoendoscopy was used to identify the pancreatic tumor, the tumor-vessel relation and for EUS-FNA to obtain tissue diagnosis. Immediately afterwards, 3D image acquisition was performed using a magnetic tracked 3D sensor. The acquisition time was 10–20 s.RESULTS: EUS results of 22 patients with solid pancreatic lesions were compared to surgical histology. This proved adenocarcinoma in 17 patients and chronic pancreatitis in 5. EUS showed VI in 10 patients, VC in 6, and no vascular involvement (NVI) in 6. Additional 3D evaluation showed VI in 6 patients, VC in 10, and NVI in 6. Surgery proved VI in 7 patients, VC in 9, and NVI in 6. EUS showed VI in 3/5 patients with chronic pancreatitis, 3D showed VC only, while surgery found two patients to have VC and with NVI. In two patients with pancreatic cancer, VI was diagnosed on two dimensional (2D), but VC on 3D evaluation. Surgery showed VC and VI in one each. In the 2D, one patient with NVI had VI on surgery; and on 3D one VC proved to have NVI at surgery. In 1/22 patients the result of 3D was false negative, while 4/22 were false positives and one false negative in conventional EUS.CONCLUSION: Linear 3D EUS seems feasible for pancreatic evaluation. In addition, linear EUS enhanced the evaluation of vascular involvement of pancreatic lesions, especially in chronic pancreatitis.(Am J Gastroenterol 2005;100:1–7) [ABSTRACT FROM AUTHOR]

When seeking to resolve complex land-management issues, geographical assessment of resources that are in short supply or in dispute can aid the communication of knowledge and the understanding among and between different stakeholders. In this paper, we illustrate how remote sensing and GIS can be used to gather and compile information regarding land-use activities and patterns among reindeer herders and other land users (forestry, mining, tourism, etc) in northern Sweden. The project represents a novel user-oriented effort largely based on the work carried out by the principal end user, i.e. the reindeer herders themselves. The basis for development of land-use plans for reindeer husbandry, was the following: to collect and digitally systemize traditional ecological and landscape knowledge of reindeer habitat use; to integrate this information with results from field inventories and satellite-based vegetation classifications; to map activities of other land users. The resulting land-use plans provide information that can facilitate consultation between the reindeer herders and other stakeholders and can facilitate operational work in reindeer management. This project can serve as a model for participatory involvement and planning, bringing indigenous knowledge and advanced remote-sensing techniques together in an interactive process. [ABSTRACT FROM AUTHOR]

Context: Computer use is increasingly common among many working populations, and concern exists about possible adverse effects of computer use, such as carpal tunnel syndrome (CTS). Objectives: To estimate the prevalence and incidence of possible CTS and to evaluate the contribution of use of mouse devices and keyboards to the risk of possible CTS. Design and Setting: A 1-year follow-up study with questionnaires conducted in 2000 and 2001 at 3500 workplaces in Denmark, followed on each of the 2 occasions by a clinical interview on symptom distribution and frequency. Participants: The questionnaire was sent to 9480 members of a trade union, with an initial response rate of 73% (n = 6943), and 82% (n = 5658) at follow-up. Main Outcome Measures: At baseline, there were 3 outcome measures: tingling/numbness in the right hand once a week or more as reported in the questionnaire; tingling, numbness, and pain in the median nerve in the right hand confirmed by clinical interview; and tingling, numbness, and pain in the median nerve in the right hand at night confirmed by clinical interview. At 1 year of follow-up the main outcome of interest was onset of symptoms among participants who had no or minor symptoms at baseline. Results: The overall self-reported prevalence of tingling/numbness in the right hand at baseline was 10.9%. The interview confirmed that prevalence of tingling/numbness in the median nerve was 4.8%, of which about one third, corresponding to a prevalence of 1.4%, experienced symptoms at night. Onset of new symptoms in the 1-year follow-up was 5.5%. In the cross-sectional comparisons and in the follow-up analyses, there was an association between use of a mouse device for more than 20 h/wk and risk of possible CTS but no statistically significant association with keyboard use. Conclusions: The occurrence of possible CTS in the right hand was low. The study emphasizes that computer use does not pose a severe occupational hazard for developing symptoms... [ABSTRACT FROM AUTHOR]

Purpose: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection.Patients and Methods: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as "gold standard" to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients.Results: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUS-guided FNA), which gave a tissue diagnosis including tumor type, without complications.Conclusions: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small mediastinal metastases of lung cancer. CT seems necessary additionally to evaluate the pretracheal region as well as the rest of the thorax, and PET may be valuable to detect distant metastases. [ABSTRACT FROM AUTHOR]

Purpose: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection. Patients and methods: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as "gold standard" to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. Results: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUSguided FNA), which gave a tissue diagnosis including tumor type, without complications. Conclusions: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small... [ABSTRACT FROM AUTHOR]

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75% of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1496 studies involving 558743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1590 patients. The working group's general conclusions are summarised in the following points •The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. •In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. •The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. •Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these studies have also documented palliative effects in a comparably limited proportion of the patients. It is of great importance to initiate a discussion whether such treatment should be recommended cancer patients in routine health care in Sweden. •The survey shows that in the instances where the literature shows small but convincing treatment effects, the use of chemotherapy is restrictive in Sweden. It is likely that this reflects the doctors' priorities of what treatments should be offered patients in routine care. It might, however, also represent an appropriate adaptation to the fact that the favourable effects have mostly been observed in selected patients with good prognosis. The patients' decisions after open information on treatment benefit and side-effects may also contribute to a limited use. Whether the same treatment benefit would be obtained in the 'whole' group of patients is not known. If such treatment should be offered all patients without medical contraindications, according to what has been demonstrated in prospective randomised trials, the number of treatments and the cost for chemotherapy would increase substantially. •Clinical trial protocols or written guidelines should preferably be widely applied as a basis for treatment decisions and for assessment of the clinical benefit from new treatments. A greater need exists for controlled clinical trials, which, when appropriate, should also include an assessment of impact on patients' quality of life (QoL) and economic consequences in conjunction with cancer treatment. This knowledge is, particularly in the palliative situation, essential for determining future recommendations, and choosing among alternative forms of treatment. Such studies usually require international collaboration. Assessment of QoL is clearly in need of further methodological development to be able to report reliable data. •The total drug cost for chemotherapy in Sweden is estimated at approximately 280 million Swedish kronor (SEK) in 1998. This represents 4% of the costs for cancer care and 1.7% of the costs for all medicinal products in Sweden. •The cost-effectiveness of chemotherapy has been studied, but these studies are mostly of low quality. They suggest, however, that chemotherapy is cost-effective, in terms of cost per life year saved, in comparison with other well-established routine treatments in a number of other diseases. •Since the treatment of cancer is far from successful, there is a need for further research. The survey showed that only about 10% of the treatments were given within clinical trial protocols aimed at further elucidating treatment effects. This figure should be considerably higher. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for Hodgkin's disease (HD) is based on 113 scientific reports including four meta-analyses, 44 randomised studies, 18 prospective studies and 40 retrospective studies. These studies involve 69 196 patients. The conclusions reached can be summarised into the following points: •Chemotherapy is of utmost importance for the cure of HD. •At early stages, extended field radiotherapy cures most patients. For the majority of patients with relapse after radiotherapy, chemotherapy is curative and the total proportion of cured early stage patients is 75-90%. Chemotherapy in addition to extended field radiotherapy reduces recurrences but does not improve long-term survival. •In early stage HD with a large mediastinal mass and/or with systemic symptoms, combined treatment with chemotherapy and radiotherapy is recommended. •It is likely that chemotherapy will play a greater role in the future in the treatment also of early stage patients in order to reduce late consequences from extended field radiotherapy. However, this conclusion remains to be better documented in the literature. •At advanced stages, chemotherapy or a combination of chemotherapy and limited field radiotherapy are effective treatment options and, using the regimens available 10-20 years ago, 40-50% of the patients are cured. Based upon more favourable short-term (three to eight years) results of more recently developed regimens, it can be expected that today a higher proportion of the patients will become long-term survivors. •Several chemotherapy regimens containing four to eight drugs are effective in HD. The best regimen considering both antitumour activity and acute and late side-effects is not known. The choice of regimen is probably best done after considering various pre-treatment factors such as the number of poor prognostic signs, concomitant diseases and individual preferences. •The results of chemotherapy are more favourable in young than in elderly patients. The development of less toxic but still effective treatment programmes is therefore particularly important for the elderly. •High dose chemotherapy with stem cell support is presently often used in patients who are chemotherapy induction failures, who relapse after a short initial remission or after a longer initial remission and treated initially with seven or eight drugs, or who have had multiple relapses. However, this use is based on data from uncontrolled or small controlled studies, not being fully convincing with respect to effect on survival. •Persistent side-effects of treatment are common among long-term survivors, although most patients have an apparently normal life. The relative contributions of chemotherapy and radiotherapy to the persistent effects are not well documented. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on aggressive, high grade non-Hodgkin's lymphoma (NHL), chiefly diffuse large B-cell lymphomas, is based on 111 scientific articles, including 35 randomised trials, 44 prospective studies and 11 retrospective studies, including totally 21 830 treated patients. The conclusions reached can be summarised into the following points: •For patients with localised aggressive NHL (stage I and non-bulky II) a combination of chemo- and radiotherapy will result in cure for a large proportion of patients. For a subgroup of patients with stage I non-bulky disease and without risk factors, local radiotherapy alone is also adequate treatment. •For patients with disseminated aggressive NHL, including the elderly, the CHOP-regimen remains the standard primary chemotherapy. In an unselected population, this treatment cures about one third of the patients. •For most patients with poor prognostic factors, CHOP provides insufficient results. The results of therapy with dose-intensive combinations of cytotoxic drugs have been conflicting. Most randomised studies, using intensive regimens as first line therapy, have failed to show any benefit in comparison to CHOP. However, it is possible that regimens other than CHOP might be more beneficial in subgroups with 'high risk' disease. This remains to be investigated in prospective studies. •In young, poor prognosis, patients a further intensified induction therapy requiring haematopetic stem cell support, i.e. high dose therapy, has been suggested to be beneficial. The best results have been reported from studies with full course standard induction followed by high-dose therapy. However, the study data are conflicting, which is why additional controlled studies are recommended. •In patients refractory to or relapsing after initial therapy, different chemotherapy combinations may induce a new response. The responses are, however, rather short-lived and long-term survival is rarely seen. •In patients not attaining complete remission after initial standard therapy, high-dose therapy with stem cell support may improve the response, but the impact on survival is not established. •In patients refractory to initial standard therapy there is no evidence for a survival prolongation from high-dose therapy with stem cell support, although a subset of patients might benefit. •For patients with chemosensitive relapse, salvage therapy followed by high-dose therapy with stem cell support is recommended, since this may result in prolonged survival. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for indolent non-Hodgkin's lymphoma (NHL), predominantly follicular lymphoma, is based on 108 scientific reports including 31 randomised studies, 38 prospective studies and 18 retrospective studies. These studies involve 8 699 patients. The conclusions reached can be summarized into the following points: In initially localized disease •The addition of chemotherapy to radiotherapy as primary treatment has not convincingly prolonged remission duration or survival. In initially advanced disease •Alkylating agents are useful palliative treatment options which can result in improved well-being for most patients, often for long periods. Combinations of chemotherapy have not convincingly resulted in more or longer remissions. •There is no proof that initial combination chemotherapy will prolong survival in comparison with single drugs. •The addition of interferon to initial combination chemotherapy may increase the response rate, significantly prolong remission duration, but prolonged survival has not been unequivocally proven. •In the absence of disease-related symptoms, treatment can safely be deferred. For patients with relapsed lymphoma •Patients may repeatedly respond to alkylating agents or combinations containing an alkylating agent, although the proportion responding decreases with each relapse. •Patients relapsing after or who are refractory to treatment with alkylating agents often respond to treatment with combinations containing an anthracycline. Responses are also often seen in patients treated with purine analogues alone or in combination with other drugs. •High dose chemotherapy followed by autologous or allogeneic reestablishment of bone marrow function can induce long-term remissions but it is not proven whether they are more frequent or of longer duration than with conventionally dosed therapy. •The impact of the novel treatment strategies including high-dose therapy on overall survival is still uncertain. •A monoclonal antibody, rituximab, is a new active substance for patients with relapsed lymphoma. It can induce remissions also in chemoresistant patients. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data from 20 randomised controlled trials and one meta-analysis. Moreover, data from 19 prospective studies, one retrospective study and four other articles were used. Totally 44 scientific articles are included, involving 11 289 patients. The conclusions reached can be summarized into the following points: •Primary treatment of patients with symptomatic B-CLL is recommended to be an oral alkylating agent such as chlorambucil. This drug induces tumour remission and symptomatic relief in a majority of patients with progressive disease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents have not been defined. •It is recommended to defer initial therapy until required by disease progression. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong survival in B-CLL patients with low tumour burden (Binet stage A). •The addition of corticosteroids to alkylator regimens has not been proven to give any benefit. •Combination chemotherapy as primary treatment has not shown any advantage compared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. •The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other drugs, they do not appear to be curative. In randomised multicentre trials a benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP or CAP) has been observed in terms of tolerance and treatment response but not yet in survival. No randomised studies have been performed to show whether one of the purine analogues should be preferred. •At relapse after single drug treatment, retreatment with the same drug often induces new remissions. However, the proportion of patients responding declines each time chlorambucil or any other single agent is readministered. •At progression on single alkylating agents, the purine analogues or various combinations, mostly CHOP, frequently induce tumour remissions. •For patients with advanced B-CLL failing to respond to fludarabine or CHOP, the prognosis is poor. None of the salvage regimens reported has produced durable remissions. •High-dose chemo-radiotherapy with stem cell transplantation has been evaluated for young patients with B-CLL. A long survival has been shown in some patients following allogeneic and autologous transplantation. However, the risk of transplantation-related mortality is still high with allo-transplants and relapse is common after auto-transplantation. A benefit of purging autologous stem cells has been proposed but evidence is lacking. Thus, transplantation remains experimental; more patients and a longer follow-up are needed to assess if cure can be achieved. •In the future an individual risk-adapted therapy will be required. The clinical heterogeneity of the disease has pointed to the necessity of new predictors for prognosis evaluated in prospective trials. [ABSTRACT FROM AUTHOR]

A breast tumour from a 65-year old woman was found to be a primary non-Hodgkin lymphoma, a very rare primary malignancy in this location. The lymphoma was of a diffuse histiocytic type according to the classification of Rappaport, or polymorphic immunocytoma according to the Kiel classification. Immunohistochemistry, not previously reported for breast lymphomas, revealed the production of IgA. In the serum this appeared as an IgA M-component which was greatly reduced after tumour removal. Immunological properties of primary breast lymphomas are reviewed, we suggest further extended studies with the immunohistochemical use of marker substances for the evaluation of prognosis. [ABSTRACT FROM AUTHOR]

Results of epidemiologic studies indicating an association between solvent exposure and the development of malignancies affecting haematopoietic and lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this association are discussed. A variety of malignant disorders have been associated with solvent exposure, i.e. acute leukaemia, Hodgkin's disease (odds ratio 2.8-6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are some indications that solvent exposure may be a risk factor for myelofibrosis. The carcinogenic effect of benzene is epidemiologically and experimentally well documeted and there are some indications that other solvents may also be hazardous. Possible mechanisms bringing about malignant transformation are discussed. The need for further epidemiologic, cytogenetic and clinical studies on the association between solvent exposure and malignant diseases is emphasised. [ABSTRACT FROM AUTHOR]

Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor, and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. These results are of interest because it has been proposed that chromosomal rearrangements may play a role in the activation of cellular oncogens. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. Although several epidemiologic studies suggest a relation between exposure to environmental agents and the development of haematological malignancies it is difficult to estimate the quantitative role of environmental hazards for this group of disorders. A closer collaboration between epidemiology, occupational medicine, haematology, oncology and cytogenetics should probably improve our knowledge about the relation between environmental factors and haematological malignancy. [ABSTRACT FROM AUTHOR]